Viral pathogenesis 1
Lecture Details Hans Netter; Week 6 MED1022; Microbiology Lecture Content Viruses are supramolecular complexes that can replicate in inappropriate cells; consist of nucleic acid in a capsid surrounded by an envelope. They can be in an extracellular state (does not carry out biosynthetic functions) - carried to its target cell; or an intracellular state where viral replication and production of new components occurs. Viruses are not living, have DNA or RNA but not both, do not contain metabolism function, do not grow or undergo division. Viruses go through attachment, penetration/entry/uncoating, gene expression/replication, assembly of structural subunits, packaging of nucleic acid, maturation and release. Arboviruses are transmitted by vectors. They are classified by nucleic acid, symmetry of capsid, presence or absence of envelope, dimensions of virion and capsid. Virion has genome, protein capsid (helical, icosahedral or complex), may have an envelope, range from 10nm to 400nm. Helix is rod shaped coat of repeating units, subunits associate with nucleic acid in a spiral or helical arrangement. Tobacco mosaic virus is a helix. Icosahedral symmetry is a solid shape with 20 triangular faces arranged around the surface of a sphere. There are 12 vertices; rotational 2-3-5 symmetry. Icosahedral or helical are surrounded by a capsid, derived from host cell membrane, contains virus encoded proteins or glycoproteins and the envelope may be flexible or unusual shapes. Complex shape is a mix of shapes with no consistent symmetry. Poxviruses are smooth rectangles in a membrane and protein layer. After infection there are early, middle and late stages of mRNA. Soon after the early stage is developed there are early, middle and late stages of protein development. After this there is self assembly, then lysis. There are many types of uncoating- can be at the plasma membrane, in the cytoplasm, within endosomes in the cell, or at the nuclear membrane. Adenovirus type 2 binds to microtubule in the cell and to the cytoplasmic phase of the nuclear pore complex. Viral genomes can be DNA, RNA or RNA to DNA. They can also be linear, circular, have unusual ends (not 5 and 3), be modified or segmented. Assembly of virus can vary. Influenza A assembles in different compartments and is released by plasma membrane budding. Viral host range is determined by attachment to host cell (receptors), presence of an appropriate vector, expression of viral genome within the cell. Tropism is that presence of cell surface receptors determines susceptibility as only permissive cells allow replication; for successful infection cells must be susceptible. Viruses can form carcinogenic cells, lytic infection, persistent infection and latent infection. RNA viruses replicate outside the nucleus, DNA replicate and assemble in the nucleus, with only capsid proteins produced outside the cell. Early gene products for DNA viruses may include DNA polymerases, proteins that bind to the origin of replication and proteins that stimulate the cell to enter the S-phase. Polyomaviridae have non-enveloped viruses; include simian virus 40; JC and BK viruses. Are 40nm, icosahedral capsid, ds DNA. These viruses have multiple uses of the same DNA via clever splicing and reading frames. It is a multifunctional protein (T protein) and a small genome with a limited number of proteins. Early transcripts include regulatory proteins, late include structural proteins. The large T antigen binds to Rb and p53, binds to SV40 ori to initiate replication, shuts off early transcription and promotes late transcription. Rb regulates G1 to S. BK and JC are resp route viruses. BK has tropism for urogenital epithelium; JC kills neural tissue in immunocompromised. Papillomavirus are non-enveloped; 55nm in diameter, icosahedral, dsDNA; circular. 16 and 18 are associated with HPV. Readings Mims 3=